Our work indicates that reasonably good delivery of water-soluble drugs, such as methotrexate and hydroxyurea to neural tissue adjacent to the CSF can be obtained when optimal CSF infusion protocols are used; however the CSF route of administration does not provide adequate distribution of cytosine arabinoside, BCNU, and thiotepa to these CNS sites. Intracarotid chemotherapy appears to offer a significant advantage in terms of increased brain uptake of drug when carotid blood flow is low or of decreased systemic delivery (drug toxicity) when the rate of metabolism and/or excretion is high. From experiments with various brain tumor systems, we have found that the amount of CSF produced within the ventricular system of a child with a choroid plexus papilloma was greatly increased and have defined some of the changes in brain transport characteristics caused by an intracranial tumor. We have demonstrated that the uses of antipyrine as an indicator of regional cerebral blood flow and of various neurotransmitter metabolite concentrations in the CSF as markers of brain metabolism are in error. The first precise measurements of spinal cord to blood transport rates of three of these metabolites were also made.